This proposal was designed to examine the effects of sex and estrogen on the self-administration of intravenously (i.v.) delivered drugs in rats. Four animal models will be used to investigate acquisition, maintenance, regulation/dysregulation, and reinstatement of drug self-administration. The effects of sex and estrogen on the acquisition of heroin, methamphetamine and d, 1-3, 4-methylenedioxymethamphetamine (MDMA) self-administration will be examined using an autoshaping procedure. A progressive ratio (PR) schedule of reinforcement and a behavioral economic analysis of demand will be used to evaluate the effects of sex and estrogen on the maintenance of cocaine and heroin self-administration. Breakpoint (BP) measures obtained on a PR schedule, along with slopes and P-max values obtained from demand curves will be used to evaluate the reinforcing efficacy of several doses of cocaine and heroin. Differential access to cocaine self-administration will be used to investigate the effect of sex on the regulation/dysregulation of cocaine intake. Dose-response curves for cocaine will be obtained to examine group differences in shifts in the dose-response curves. The effect of estrogen on the reinstatement of cocaine self-administration will be examined using a priming model of drug reinstatement in which lever pressing for drug is extinguished by replacing cocaine infusions with saline infusions. Reinstatement of responding is then tested by administering a priming injection of cocaine.